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A spotlight on dosage and subject selection for effective neuroprotection: exploring the central role of mitochondria

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Neural Regeneration Research 2025年第4期20卷 1081-1082页

作者： john Mitrofanis Jonathan Stone Michael R.Hamblin Pierre Magistretti Alim-louis Benabid Glen Jeffery Fonds Clinatec UniversitéGrenoble AlpesGrenobleFrance School of Medical Science University of SydneySydneyAustralia Faculty of Health Sciences University of JohannesburgJohannesburgSouth Africa King Abdullah University of Science and Technology ThuwalSaudi Arabia Institute of Ophthalmology University College LondonLondonUK

Neurons are notoriously vulnerable cell types.Even the slightest change in their internal and/or external environments will cause much distress and dysfunction,leading often to their death.A range of pathological conditions,including stroke,head trauma,and neurodegenerative disease,can generate stress in neurons,affecting their survival and proper function.In most neural pathologies,mitochondria become dysfunctional and this plays a pivotal role in the process of cell death.The challenge over the last few decades has been to develop effective interventions that improve neuronal homeostasis under pathological conditions.Such interventions,often referred to as disease-modifying or neuroprotective,have,however,proved frustratingly elusive,at both preclinical and,in particular,clinical levels.In this perspective,we highlight two factors that we feel are key to the development of effective neuroprotective treatments.These are:firstly,the choice of dose of intervention and method of application,and secondly,the selection of subjects,whether they be patients or the animal model.

关键词： protective dosage distress

Do astrocytes respond to light,sound,or electrical stimulation?

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Neural Regeneration Research 2023年第11期18卷 2343-2347页

作者： Audrey Le Naour Emilien Beziat Jaimie Hoh Kam Pierre Magistretti Alim-louis Benabid john Mitrofanis UniversitéGrenoble Alpes Fonds de dotationClinatecGrenobleFrance King Abdullah University of Science and Technology ThuwalSaudi Arabia Institute of Ophthalmology University College LondonLondonUK

Astrocytes are not only the most populous cell type in the human brain,but they also have the most extensive and dive rse sets of connections,across synapses,axons,blood vessels,as well as having their own internal network.Unsurprisingly,they are associated with many brain functions;from the synaptic transmission to energy metabolism and fluid homeostasis,and from cerebral blood flow and blood-brain barrier maintenance to neuroprotection,memory,immune defenses and detoxification,slee p,and early development.And yet,notwithstanding these key roles,so many current therapeutic approaches to a range of brain disorders have largely neglected their potential involvement.In this review,we consider the role of astrocytes in three brain therapies;two are emerging treatments(photobiomodulation and ultrasound),while the other is well-established(deep brain stimulation).In essence,we explore the issue of whether external sources,such as light,sound,or electricity,can influence the function of astrocytes,as they do neurons.We find that,when taken all together,each of these external sources can influence many,if not,all of the functions associated with astrocytes.These include influencing neuronal activity,prompting neuroprotection,reducing inflammation(astrogliosis) and potentially increasing cerebral blood flow and stimulating the glymphatic system.We suggest that astrocytes,just like neurons,can respond positively to each of these external applications and that their activation co uld each impart many beneficial outcomes on brain function;they are likely to be key playe rs underpinning the mechanisms behind many therapeutic strategies.

关键词： deep brain stimulation high frequency infrared mitochondria red ultrasound

Underworld-GT Applied to Guangdong,a Tool to Explore the Geothermal Potential of the Crust

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Journal of Earth Science 2015年第1期26卷 78-88页

作者： Steve Quenette Yufei Xi john Mansour louis Moresi David Abramson Monash e Research Centre Monash UniversityClayton 3800Australia The Institute of Hydrogeology and Environmental Geology Chinese Academy of Geological Sciences School of Earth Sciences The University of MelbourneMelbourne 3010Australia Research Computing Centre The University of QueenslandSt Lucia 4072Australia

Geothermal energy potential is usually discussed in the context of conventional or engineered systems and at the scale of an individual reservoir. Whereas exploration for conventional reservoirs has been relatively easy, with expressions of resource found close to or even at the surface, exploration for non-conventional systems relies on temperature inherently increasing with depth and searching for favourable geological environments that maximise this increase. To utilitise the information we do have, we often assimilate available exploration data with models that capture the physics of the domi- nant underlying processes. Here, we discuss computational modelling approaches to exploration at a regional or crust scale, with application to geothermal reservoirs within basins or systems of basins. Target reservoirs have （at least） appropriate temperature, permeability and are at accessible depths. We discuss the software development approach that leads to effective use of the tool Underworld. We explore its role in the process of modelling, understanding computational error, importing and exporting geological knowledge as applied to the geological system underpinning the Guangdong Province, China.

关键词： Underworld-GT geothermal potential computational modelling approach Guangdong.

Is there a hormonal basis for human homosexuality？

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Asian Journal of Andrology 2011年第6期13卷 793-794页

作者： louis Gooren VU University Medical Center Amsterdam 1081HV The Netherlands

In the August 2011 issue of Endocrinology, Dr Balthazart presents a minireview on Hormones and Human Sexual Orientation.1 As in most scientific papers on this issue, the contribution lacks an operational definition ... 详细信息

关键词： Endocrinology Balthazart presents sexual/erotic

Post-ablation surveillance in Barrett's esophagus: A review of the literature

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World Journal of Gastroenterology 2016年第17期22卷 4297-4306页

作者： Matthew W Stier Vani J Konda john Hart irving Waxman Department of Internal Medicine The University of Chicago Medicine Division of Gastroenterology Department of Medicine The University of Chicago Medicine Department of Pathology The University of Chicago Medicine

Barrett's esophagus(BE) is a pre-malignant condition affecting up to 15% of patients with gastroesophageal reflux disease. Neoplastic Barrett's mucosa is defined as harboring high grade dysplasia or intra-mucosal cancer, and carries a high risk of progression to esophageal adenocarcinoma. The rising incidence of Barrett's lesions along with the high morbidity of surgical approaches has led to the development of numerous validated endoscopic techniques capable of eradicating neoplastic mucosa in a minimally invasive manner. While there has been widespread adoption of these techniques, less is known about optimal surveillance intervals in the post-therapy period. This is due in part to limitations in current surveillance methods, questions about durability of treatment response and the risk of subendothelial progression. As we are now able to achieve organ sparing eradication of superficial neoplasia in BE, we need to also then focus our attention on how best to manage these patients after eradication is achieved. Implementing optimal surveillance practices requires additional understanding of the biology of the disease, appreciation of the limits of current tools and treatments, and exploration of the role of adjunctive technologies. The aim of this article is to provide a comprehensive review of current literature surrounding post-ablation surveillance in neoplastic BE.

关键词： Barrett’s esophagus Endotherapy Postablation surveillance Neoplastic Radiofrequency ablation Endosco

Application of established pathophysiologic processes brings greater clarity to diagnosis and treatment of hyponatremia

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World Journal of Nephrology 2017年第2期6卷 59-71页

作者： john K Maesaka louis J Imbriano Nobuyuki Miyawaki Department of Medicine and Division of Nephrology and Hypertension Winthrop-University Hospital

Hyponatremia, serum sodium < 135 m Eq/L, is the most common electrolyte abnormality and is in astate of flux. Hyponatremic patients are symptomatic and should be treated but our inability to consistently determine the causes of hyponatremia has hampered the delivery of appropriate therapy. This is especially applicable to differentiating syndrome of inappropriate antidiuresis(SIAD) from cerebral salt wasting(CSW) or more appropriately, renal salt wasting(RSW), because of divergent therapeutic goals, to water-restrict in SIAD and administer salt and water in RSW. Differentiating SIAD from RSW is extremely difficult because of identical clinical parameters that define both syndromes and the mindset that CSW occurs rarely. It is thus insufficient to make the diagnosis of SIAD simply because it meets the defined characteristics. We review the pathophysiology of SIAD and RSW, the evolution of an algorithm that is based on determinations of fractional excretion of urate and distinctive responses to saline infusions to differentiate SIAD from RSW. This algorithm also simplifies the diagnosis of hyponatremic patients due to Addison's disease, reset osmostat and prerenal states. It is a common perception that we cannot accurately assess the volume status of a patient by clinical criteria. Our algorithm eliminates the need to determine the volume status with the realization that too many factors affect plasma renin, aldosterone, atrial/brain natriuretic peptide or urine sodium concentration to be useful. Reports and increasing recognition of RSW occurring in patients without evidence of cerebral disease should thus elicit the need to consider RSW in a broader group of patients and to question any diagnosis of SIAD. Based on the accumulation of supporting data, we make the clinically important proposal to change CSW to RSW, to eliminate reset osmostat as type C SIAD and stress the need for a new definition of SIAD.

关键词：低钠血症电解质治疗方法临床分析

Use of volumetric laser endomicroscopy for dysplasia detection at the gastroesophageal junction and gastric cardia

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World Journal of Gastrointestinal Endoscopy 2017年第7期9卷 319-326页

作者： Nina Gupta Uzma Siddiqui irving Waxman Christopher Chapman Ann Koons Vesta Valuckaite Shu-Yuan Xiao Namrata Setia john Hart Vani Konda Department of Medicine University of Chicago Medical Center Center of Endoscopic Research and Therapeutics Department of MedicineUniversity of Chicago Medical Center Department of Pathology University of Chicago Medical Center

AIM To determine specific volumetric laser endomicroscopy(VLE) imaging features associated with neoplasia at the gastroesophageal junction(GEJ) and gastric cardia.METHODS During esophagogastroduodenoscopy for patients with known or suspected Barrett's esophagus,VLE was performed before biopsies were taken at endoscopists' discretion.The gastric cardia was examined on VLE scan from the GEJ(marked by top of gastric folds) to 1 cm distal from the GEJ.The NineP oints VLE console was used to analyze scan segments for characteristics previously found to correlate with normal or abnormal mucosa.Glands were counted individually.Imaging features identified on VLE scan were correlated with biopsy results from the GEJ and cardia region.RESULTS This study included 34 cases.Features characteristic of the gastric cardia(gastric rugae,gastric pit architecture,poor penetration) were observed in all(100%) scans.Loss of classic gastric pit architecture was common and there was no difference between those with neoplasia and without(100% vs 74%,P = NS).The abnormal VLE feature of irregular surface was more often seen in patients with neoplasia than those without(100% vs 18%,P < 0.0001),as was heterogeneous scattering(86% vs 41%,P < 0.005) and presence of anomalous glands(100% vs 59%,P < 0.05).The number of anomalous glands did not differ between individual histologic subgroups(ANOVA,P = NS).CONCLUSION The transition from esophagus to gastric cardia is reliably identified on VLE.Histologically abnormal cardia mucosa produces abnormal VLE features.Optical coherence tomography algorithms can be expanded for use at the GEJ/cardia.

关键词：容量的激光 endomicroscopy 贲门 Gastroesophageal 连接 Barretts 光连贯断层摄影术瘤形成

Dilemmas in end-stage heart failure

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Journal of Geriatric Cardiology 2015年第1期12卷 57-65页

作者： Carol Chen-Scarabelli louis Saravolatz Benjamin Hirsh Pratik Agrawal Tiziano M. Scarabelli Veterans Affairs Healthcare System Ann Arbor 2215 Fuller Rd. Ann Arbor M148105 USA St. john Hospital and Medical Center~Wayne State University 22101 Moross Rd. Detroit M148236 USA Zena and Michael A. Wiener Cardiovascular Institute Mount Sinai Medical Center One Gustave L. Levy Place Box 1030 New York NY 10029-6574 USA

心失败(HF ) ，复杂临床的症候群由于结构或心的机能紊乱，是一个主要全球健康问题，与在 USA 的超过 580 万的流行独自，并且过去 2300 万世界范围。作为在 65 岁以上的病人之中的住院的一个领先的原因， HF 是保健资源的一个主要消费... 详细信息

心失败(HF ) ，复杂临床的症候群由于结构或心的机能紊乱，是一个主要全球健康问题，与在 USA 的超过 580 万的流行独自，并且过去 2300 万世界范围。作为在 65 岁以上的病人之中的住院的一个领先的原因， HF 是保健资源的一个主要消费者，创造保健系统上的实质的紧张。这份报纸在结束阶段 HF 照顾讨论 HF，金融影响，和 multifaceted 困境的传染病学。搜索用象结束阶段心失败那样的关键词在药网站(www.***.gov ) 的美国国家图书馆上被进行，辩解的照顾，道德的窘境。尽管有 HF 的差的预后(比那更坏为许多癌症) ，许多 HF 病人， caregivers，和临床医生不知道差的预后。另外， HF 的无法预言的临床的轨道复杂化计划 end-of-life 照顾，例如辩解的照顾和供旅客休息的招待所，导致如此的资源的 underutilization。在结论，在结束阶段 HF 的道德的窘境是众多的，使不仅病人，而且 caregiver 卷入，保健队，和社会。

关键词：心脏末期衰竭医疗保健系统图书馆网站护理人员资源利用功能障碍

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